Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells

J Leukoc Biol. 2017 Apr;101(4):901-911. doi: 10.1189/jlb.3MA0616-287R. Epub 2016 Nov 23.


The interleukin (IL)-1 family member IL-37 is one of few anti-inflammatory cytokines, and it is capable of countering a broad spectrum of proinflammatory assaults. Although it is known that leukocytes are a major source of IL-37, knowledge on IL-37 production and secretion in specific immune cell types remains limited. Thus, we investigated IL-37 mRNA expression as well as protein production and secretion in human PBMCs. In PBMCs stimulated with agonists of Toll-like receptors (TLRs) 1-6 and 9, IL1F7 (the IL-37-encoding gene) was induced up to 9-fold, peaked at 6-8 h and returned to steady-state at 72 h. LPS-induced IL1F7 expression comprised isoforms b and c but not a and e Flow cytometry revealed that among IL-37+ PBMCs, monocytes predominated (81-91%), but T cells (6-8%) and myeloid dendritic cells (mDCs, 1-2%) also contributed to the IL-37+ leukocyte pool. Monocytes and mDCs, but not T cells, were capable of secreting IL-37. Whereas monocytes and mDCs secreted IL-37 upon LPS stimulation, only mDCs also released IL-37 at steady-state. Among monocyte subsets, IL-37 was LPS inducible and secreted only in classical and, although less pronounced, in intermediate monocytes; secretion was observed as early as 3 h after stimulation. Overall, our data suggest that constitutive IL-37 secretion by mDCs may serve to maintain an anti-inflammatory milieu at steady state, whereas IL-37 is stored in monocytes to be available for rapid release upon inflammatory encounters, thus acting as a novel anti-inflammatory alarmin. These insights may prove important to advancing towards clinical use the protective functions of one of the most powerful anti-inflammatory mediators so far discovered.

Keywords: alarmin; cytokine secretion; isoform; peripheral blood mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Humans
  • Interleukin-1 / metabolism*
  • Kinetics
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Toll-Like Receptors / metabolism


  • IL37 protein, human
  • Interleukin-1
  • Ligands
  • Lipopolysaccharides
  • Toll-Like Receptors